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In detoxified alcohol-dependent patients, alcohol-related stimuli can promote
relapse. However, to date, the mechanisms by which contextual stimuli promote
relapse have not been elucidated in detail. One hypothesis is that such
contextual stimuli directly stimulate the motivation to drink via associated
brain regions like the ventral striatum and thus promote alcohol seeking, intake
and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those
behavioral phenomena contributing to relapse, capturing how Pavlovian
conditioned (contextual) cues determine instrumental behavior (e.g. alcohol
seeking and intake). We used a PIT paradigm during functional magnetic resonance
imaging to examine the effects of classically conditioned Pavlovian stimuli on
instrumental choices in n=31 detoxified patients diagnosed with alcohol
dependence and n=24 healthy controls matched for age and gender. Patients were
followed up over a period of 3 months. We observed that (1) there was a
significant behavioral PIT effect for all participants, which was significantly
more pronounced in alcohol-dependent patients; (2) PIT was significantly
associated with blood oxygen level-dependent (BOLD) signals in the nucleus
accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc
activation was associated with, and predictive of, critical outcomes (amount of
alcohol intake and relapse during a 3 months follow-up period) in
alcohol-dependent patients. These observations show for the first time that
PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on
instrumental behavior, predict alcohol intake and relapse in alcohol dependence.